IHH Indian hedgehog signaling molecule [Homo sapiens (human)] - Gene

Summary

Official Symbol: IHHprovided by HGNC
Official Full Name: Indian hedgehog signaling moleculeprovided by HGNC
Primary source: HGNC:HGNC:5956
See related: Ensembl:ENSG00000163501 MIM:600726; AllianceGenome:HGNC:5956
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BDA1; HHG2
Summary: This gene encodes a member of the hedgehog family of proteins. The encoded preproprotein is proteolytically processed to generate multiple protein products, including an N-terminal fragment that is involved in signaling. Hedgehog family proteins are essential secreted signaling molecules that regulate a variety of developmental processes including growth, patterning and morphogenesis. The protein encoded by this gene specifically plays a role in bone growth and differentiation. Mutations in this gene are the cause of brachydactyly type A1, which is characterized by shortening or malformation of the fingers and toes. Mutations in this gene are also the cause of acrocapitofemoral dysplasia. [provided by RefSeq, Nov 2015]
Expression: Biased expression in endometrium (RPKM 15.6), colon (RPKM 13.1) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q35

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (219054424..219060921, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (219542768..219549269, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (219919146..219925643, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis.
Title: Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis.
Acrocapitofemoral dysplasia: Novel mutation in IHH in two adult patients from the third family in the literature and progression of the disease.
Title: Acrocapitofemoral dysplasia: Novel mutation in IHH in two adult patients from the third family in the literature and progression of the disease.
Highly Conserved C-Terminal Region of Indian Hedgehog N-Fragment Contributes to Its Auto-Processing and Multimer Formation.
Title: Highly Conserved C-Terminal Region of Indian Hedgehog N-Fragment Contributes to Its Auto-Processing and Multimer Formation.
Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway.
Title: Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway.
Clinical and Molecular Description of 16 Families With Heterozygous IHH Variants.
Title: Clinical and Molecular Description of 16 Families With Heterozygous IHH Variants.
HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells.
Title: HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells.
the levels of SHH and IHH proteins were significantly correlated with the expression of proteins involved in the TGF-b1 pathway. Moreover, the expression of the HH pathway ligands was positively associated with the expression of TAZ, supporting the notion that TAZ may play a role in the activation of the HH pathway thereby regulating the expression of its ligands
Title: Downregulation of hedgehog ligands in human simple steatosis may protect against nonalcoholic steatohepatitis: Is TAZ a crucial regulator?
Report of a five-generation Chinese family with Brachydactyly type A1 (BDA-1) due to a novel pathogenic variant (c.299A > G (p.D100G)) of IHH; this expands the clinical and genetic spectrum of BDA-1.
Title: A novel variant of IHH in a Chinese family with brachydactyly type 1.
The Roles of Indian Hedgehog Signaling in TMJ Formation.
Title: The Roles of Indian Hedgehog Signaling in TMJ Formation.
pathogenesis of BDA1 and the role of IHH signaling in chondrogenesis
Title: p.E95K mutation in Indian hedgehog causing brachydactyly type A1 impairs IHH/Gli1 downstream transcriptional regulation.

Submit: New GeneRIF Correction See all GeneRIFs (84)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Acrocapitofemoral dysplasia MedGen: C1843096 OMIM: 607778 GeneReviews: Not available	Compare labs
Brachydactyly type A1A MedGen: CN295859 OMIM: 112500 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 20 loci that influence adult height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Many sequence variants affecting diversity of adult human height. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:511564 (e-PCR)
- UniSTS:157511

SGC35345 (e-PCR)
- UniSTS:54623

RH78911 (e-PCR)
- UniSTS:54624

IHH_7807 (e-PCR)
- UniSTS:468068

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables cholesterol-protein transferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables patched binding	IBA Inferred from Biological aspect of Ancestor more info
enables patched binding	IDA Inferred from Direct Assay more info	PubMed
enables patched binding	IPI Inferred from Physical Interaction more info	PubMed
enables peptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in bone resorption	IEA Inferred from Electronic Annotation more info
involved_in branching involved in blood vessel morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in camera-type eye photoreceptor cell fate commitment	IEA Inferred from Electronic Annotation more info
involved_in cell fate specification	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell maturation	IEA Inferred from Electronic Annotation more info
involved_in cell-cell signaling	IEA Inferred from Electronic Annotation more info
involved_in chondrocyte differentiation involved in endochondral bone morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in chondrocyte proliferation	IEA Inferred from Electronic Annotation more info
involved_in embryonic camera-type eye morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic digestive tract morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic pattern specification	IEA Inferred from Electronic Annotation more info
involved_in embryonic skeletal joint development	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell-cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in head morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in heart looping	ISS Inferred from Sequence or Structural Similarity more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in intein-mediated protein splicing	IEA Inferred from Electronic Annotation more info
involved_in liver regeneration	IEA Inferred from Electronic Annotation more info
involved_in maternal process involved in female pregnancy	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of T cell differentiation in thymus	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of alpha-beta T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of eye pigmentation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of immature T cell proliferation in thymus	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron development	IEA Inferred from Electronic Annotation more info
involved_in osteoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in pancreas development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell differentiation in thymus	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of alpha-beta T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of collagen biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of mesenchymal cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein autoprocessing	IEA Inferred from Electronic Annotation more info
involved_in proteoglycan metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of gene expression	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of growth	IEA Inferred from Electronic Annotation more info
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
involved_in response to mechanical stimulus	IEA Inferred from Electronic Annotation more info
involved_in retinal pigment epithelium development	IEA Inferred from Electronic Annotation more info
involved_in self proteolysis	ISS Inferred from Sequence or Structural Similarity more info
involved_in skeletal system development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in smooth muscle tissue development	IEA Inferred from Electronic Annotation more info
involved_in smoothened signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in smoothened signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in somite development	ISS Inferred from Sequence or Structural Similarity more info
involved_in vitelline membrane formation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular matrix	IEA Inferred from Electronic Annotation more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: indian hedgehog protein

Names: Indian hedgehog homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016741.2 RefSeqGene

Range

5000..11497

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002181.4 → NP_002172.2 indian hedgehog protein preproprotein

See identical proteins and their annotated locations for NP_002172.2

Status: REVIEWED

Source sequence(s)

AC097468

Consensus CDS

CCDS33380.1

UniProtKB/Swiss-Prot

B9EGM5, O43322, Q14623, Q8N4B9

Related

ENSP00000295731.5, ENST00000295731.7

Conserved Domains (3) summary

cd00081
Location:203 → 347

Hint; Hedgehog/Intein domain, found in Hedgehog proteins as well as proteins which contain inteins and undergo protein splicing (e.g. DnaB, RIR1-2, GyrA and Pol). In protein splicing an intervening polypeptide sequence - the intein - is excised from a protein, ...

pfam01079
Location:192 → 386

Hint; Hint module

pfam01085
Location:44 → 189

HH_signal; Hedgehog amino-terminal signalling domain